Dr Deaglan McCullough

High carbohydrate, lower fat (HCLF) diets are recommended to reduce cardiometabolic disease (CMD) but low carbohydrate high fat (LCHF) diets can be just as effective. The effect of LCHF on novel insulin resistance biomarkers and the metabolome has not been fully explored. The aim of this study was to investigate the impact of an ad libitum 8-week LCHF diet compared with a HCLF diet on CMD markers, the metabolome, and insulin resistance markers. n = 16 adults were randomly assigned to either LCHF (n = 8, <50 g CHO p/day) or HCLF diet (n = 8) for 8 weeks. At weeks 0, 4 and 8, participants provided fasted blood samples, measures of body composition, blood pressure and dietary intake. Samples were analysed for markers of cardiometabolic disease and underwent non-targeted metabolomic profiling. Both a LCHF and HCLF diet significantly (p < 0.01) improved fasting insulin, HOMA IR, rQUICKI and leptin/adiponectin ratio (p < 0.05) levels. Metabolomic profiling detected 3489 metabolites with 78 metabolites being differentially regulated, for example, an upregulation in lipid metabolites following the LCHF diet may indicate an increase in lipid transport and oxidation, improving insulin sensitivity. In conclusion, both diets may reduce type 2 diabetes risk albeit, a LCHF diet may enhance insulin sensitivity by increasing lipid oxidation.

Background COVID-19 lockdown measures led to the suspension of centre-based cardiac rehabilitation (CR). We aimed to describe the impact of lockdown on CR behaviours and perceptions of efficacy in a sample of CR participants. Methods An online survey was conducted amongst CR participants from May to October 2020, COVID-19-related lockdown restrictions. Anthropometric data, participant-determined levels of motivation and self-perceived efficacy, CR practices etc., pre- and post-lockdown, were collected. Results The probability of practicing CR in public gyms and hospitals decreased 15-fold (47.2% pre-, 5.6% post-lockdown; OR[95% CI] 0.065[0.013; 0.318], p < 0.001), and 34-fold (47.2% pre, 2.8% post; OR[95% CI] 0.029[0.004; 0.223], p < 0.001), respectively. Amongst participants, 79.5% indicated that their CR goals had changed and were 78% less likely to engage in CR for socialization after lockdown (47.2% pre, 16.7% post; OR[95% CI] 0.220[0.087; 0.555]; p = 0.002). The probability of receiving in-person supervision decreased by 90% (94.4% pre, 16.7% post; OR[95% CI] 0.011[0.002; 0.056]), while participants were almost 7 times more likely to use online supervision (11.1% pre, 44.4% post; OR[95% CI] 6.824[2.450; 19.002]) (both p < 0.001). Fifty percent indicated that their enjoyment of CR was lower than before lockdown and 27.8% reported they would be less likely to continue with CR in the newer format. Conclusions Lockdown was associated with considerable changes in how CR was practiced, motivation levels and willingness to continue with CR. Further research is warranted to develop and improve strategies to implement in times when individuals cannot attend CR in person and not only during pandemics.

BACKGROUND: Cardiac rehabilitation (CR) is an essential component of long-term recovery following a cardiac event. Typical CR may not be optimal for patients presenting with sarcopenic obesity (SO) who present with reduced muscle mass and elevated adipose tissue, and may indicate greater cardiovascular disease (CVD) risk. Resistance exercise and high-protein diets are known to increase muscle mass, while Mediterranean-style diets have been shown to reduce CVD risk. A high-protein Mediterranean-style diet combined with resistance exercise intervention is yet to be trialled in cardiac rehabilitation populations. OBJECTIVES: Primary outcome: to determine the feasibility of such an intervention by investigating the perceptions, acceptance and adherence to a resistance exercise protocol and high-protein Mediterranean style diet in a UK cardiac rehabilitation population with SO. Secondary outcome: to trial this protocol ahead of a fully powered clinical study. METHODS: Eligible cardiac rehabilitation patients will be randomised to one of the following: 1) a control group (standard CR), 2) high-protein Mediterranean-style diet, 3) resistance exercise group, or 4) both high-protein Mediterranean-style diet and resistance exercise group. The pilot study will last 12 weeks. Measures of body composition (dual energy x-ray absorptiometry) grip strength, CVD risk (e.g., fasting triglycerides, glucose, cholesterol) and dietary adherence will be assessed at baseline and after 12 weeks. To compare groups, a mixed model ANOVA (time x intervention) will be performed. Patient participant involvement throughout the development of this project will be used to determine the feasibility of a future, fully powered, randomised control trial. A feasibility questionnaire will help establish the proportion of eligible participants, their willingness to be randomised, response rates, and ethical considerations. Furthermore, focus groups, food tasting and telephone interviews will be conducted to assess the acceptability of recipes and exercise protocols provided. DISCUSSION: This pilot trial will determine whether a fully powered, multi-centred randomised control trial in CR patients with SO can be implemented. The information received from patient involvement will be invaluable for identifying possible barriers to participation and tailoring interventions to participant needs, helping to increase the likelihood of long-term compliance to health-promoting lifestyle changes. REGISTRATION: This study is registered at clinicaltrials.gov (NCT04272073), registered on 17/02/2020, https://clinicaltrials.gov/ct2/show/NCT04272073. DATE AND VERSION: 28/12/20 version 3.0.

The COVID-19 pandemic is an extraordinary global emergency that has led to the implementation of unprecedented measures in order to stem the spread of the infection. Internationally, governments are enforcing measures such as travel bans, quarantine, isolation, and social distancing leading to an extended period of time at home. This has resulted in reductions in physical activity and changes in dietary intakes that have the potential to accelerate sarcopenia, a deterioration of muscle mass and function (more likely in older populations), as well as increases in body fat. These changes in body composition are associated with a number of chronic, lifestyle diseases including cardiovascular disease (CVD), diabetes, osteoporosis, frailty, cognitive decline, and depression. Furthermore, CVD, diabetes, and elevated body fat are associated with greater risk of COVID-19 infection and more severe symptomology, underscoring the importance of avoiding the development of such morbidities. Here we review mechanisms of sarcopenia and their relation to the current data on the effects of COVID-19 confinement on physical activity, dietary habits, sleep, and stress as well as extended bed rest due to COVID-19 hospitalization. The potential of these factors to lead to an increased likelihood of muscle loss and chronic disease will be discussed. By offering a number of home-based strategies including resistance exercise, higher protein intakes and supplementation, we can potentially guide public health authorities to avoid a lifestyle disease and rehabilitation crisis post-COVID-19. Such strategies may also serve as useful preventative measures for reducing the likelihood of sarcopenia in general and in the event of future periods of isolation.

It is estimated 6.4% of males and 1.6% of females globally use anabolic-androgenic steroids (AAS), mostly for appearance and performance enhancing reasons. In combination with resistance exercise, AAS use increases muscle protein synthesis resulting in skeletal muscle hypertrophy and increased performance. Primarily through binding to the androgen receptor, AAS exert their hypertrophic effects via genomic, non-genomic and anti-catabolic mechanisms. However, chronic AAS use also has a detrimental effect on metabolism ultimately increasing the risk of cardiovascular disease (CVD). Much research has focused on AAS effects on blood lipids and lipoproteins, with abnormal concentrations of these associated with insulin resistance, hypertension and increased visceral adipose tissue (VAT). This clustering of interconnected abnormalities is often referred as metabolic syndrome (MetS). Therefore, the aim of this review is to explore the impact of AAS use on mechanisms of muscle hypertrophy and markers of MetS. AAS use markedly decreases high-density lipoprotein cholesterol (HDL-C) and increases low-density lipoprotein cholesterol (LDL-C). Chronic AAS use also appears to cause higher fasting insulin levels and impaired glucose tolerance and possibly higher levels of VAT; however, research is currently lacking on the effects of AAS use on glucose metabolism. While cessation of AAS use can restore normal lipid levels, it may lead to withdrawal symptoms such as depression and hypogonadism that can increase CVD risk. Research is currently lacking on effective treatments for withdrawal symptoms and further long-term research is warranted on the effects of AAS use on metabolic health in males and females.

Worldwide, cardiovascular disease (CVD) is the number 1 cause of mortality and is associated with insulin resistance (IR). Emerging biomarkers such as FGF21 and adiponectin are associated with cardiometabolic risk. Low carbohydrate, high fat (LCHF) diets have been reported to reduce cardiometabolic risk markers; however, few studies have compared a LCHF diet vs. a high carbohydrate (HC), lower fat diet under ad libitum conditions on adiponectin and FGF21. The purpose of this study was to investigate the effects of an ad libitum LCHF vs. HC diet on IR, FGF21 and adiponectin in 16 healthy adults. Ethical approval: Liverpool John Moores University Research Ethics Committee (16/ELS/029); registered with ClinicalTrials.gov (Ref. NCT03257085). Participants were randomly assigned to a HC diet (n = 8, the UK Eatwell guidelines; ≥ 50% of energy from carbohydrates) or a LCHF diet (n = 8, consume < 50 g/day of carbohydrates). All provided plasma samples at 0, 4 and 8 weeks. FGF21 (R&D Systems) was analysed via ELISA and adiponectin, insulin and glucose were analysed via immunoassay technology (Randox Evidence Investigator™ Metabolic Syndrome Arrays I & II). Mann Whitney, Friedmans, Wilcoxon tests and 2×3 ANOVA (IBM SPSS 25®) were undertaken to investigate significant differences between and within groups. The homeostatic model assessment (HOMA) was used to calculate IR. FGF21 significantly (P = 0.04) decreased (Mdn, IQR:148.16, 78.51–282.02 to 99.4, 39.87–132.29 pg/ml) after 4 weeks and significantly (P = 0.02) increased (Mdn, IQR:167.38, 80.82–232.89 pg/ml) by 8 weeks vs. baseline with LCHF. No significant differences (P > 0.05) were observed between groups. Adiponectin was significantly (P = 0.03) different at week 4 only between groups. Adiponectin increased after 4 weeks (Mdn, IQR:13.44, 9.12–25.47 to 16.64, 11.96–21.51 ng/ml) but was only significantly (P = 0.03) different by 8 weeks vs. baseline in the HC group (Mdn, IQR:16, 10.8–27.43 ng/ml). Adiponectin remained unchanged (P = 0.96) in the LCHF group. HOMA significantly decreased with both diets after 8 weeks only (mean ± SD, LCHF: 2.9 ± 1.3 to 1.8 ± 0.8, HC: 2.5 ± 0.6 to 1.9 ± 0.6, P = 0.008) but was not significantly (P = 0.60) different between groups. These preliminary data reveal that while both diets improved insulin sensitivity, they may do so by different mechanisms. Future studies are warranted to investigate further, how a LCHF vs. HC diet affects FGF21 and adiponectin, and the subsequent regulation of IR. Furthermore, studies that extend these findings by determining the impact of LCHF vs. HC on peripheral metabolism to determine potential nutrition-mediated mechanisms of metabolic adaptation are warranted.

Abstract

Apolipoproteins (apo) regulate lipoprotein characteristics and lipid metabolism. ApoC-III is a regulator of triglyceride-rich lipoprotein (TRL) metabolism and apolipoproteins are important biomarkers for cardiovascular disease (CVD) risk prediction. A low carbohydrate high fat (LCHF) diet improves cardiometabolic risk, especially via reduction of TRL. However, few studies have compared a LCHF vs. a high carbohydrate (HC), lower fat diet under ad libitum conditions on apoC-III levels. The objectives of this investigation were to measure the effect of a LCHF vs. a HC diet on apoC-III, apoA1, apoB and apoB/apoA1 in 16 healthy Caucasian adults aged 19–64. Ethical approval: Liverpool John Moores University Research Ethics Committee (16/ELS/029); registered with ClinicalTrials.gov (Ref. NCT03257085). Participants randomly assigned to a HC diet (UK Eatwell guidelines; ≥ 50% of energy from carbohydrates) (n = 8), or a LCHF diet (consume < 50 g/day of carbohydrates) (n = 8) provided plasma samples at 0, 4 and 8 weeks. ApoA1 and apoB were analysed by an automated chemistry analyser (Daytona, Randox Laboratories Ltd, UK). ApoC-III was analysed via ELISA (Thermo Fisher Ltd, USA). Factorial 2×3 ANOVA and ANCOVA (IBM SPSS 25®) were undertaken to investigate significant differences and to control for variables influenced by baseline measures and visceral adipose tissue (VAT). Results show 0, 4, and 8 weeks respectively: ApoC-III (LCHF: 19.12 ± 9.14, 16.05 ± 7.95, 15.11 ± 3.17 mg/dl; HC: 22.13 ± 8.38, 28.22 ± 13.85, 22.22 ± 7.7 mg/dl) showed no significant (P = 0.319) change. No significant (P = 0.23) change was also observed in ApoB (LCHF: 107.25 ± 20.35, 111.38 ± 24.81, 111.43 ± 19.93 mg/dl; HC: 94.38 ± 20.79, 105.00 ± 20.13, 99.00 ± 29.09 mg/dl). Similarly apoA1 (LCHF: 158.71 ± 14.27, 166.50 ± 23.09, 173.00 ± 29.42 mg/dl; HC: 164.71 ± 30.25, 172.50 ± 29.44, 174.00 ± 32.83 mg/dl) showed no significant change (P = 0.76). This resulted in a relatively unchanged apoB/A1 throughout the study in both diets (P = 0.30). No significant (P > 0.05) differences were found after 4 weeks or between groups also. ANCOVA revealed a trend (P = 0.06) in apoC-III for a difference between groups (LCHF: Δ-6.6 mg/dl vs. HC: Δ1.2 mg/dl) after 8 weeks but no significant (P > 0.05) changes in other apolipoproteins were detected. These preliminary data reveal that a LCHF diet does not improve the apolipoprotein profile; however, when accounting for other metabolic risk factors (i.e. VAT) there was a trend towards lowering apoC-III levels (P = 0.06). Modulation of apoC-III may lead to improved lipid metabolism, but higher-powered studies are warranted before any improvement on CVD risk can be inferred.

Metabolic diseases are the leading global causes of death(1).Low carbohydrate, high fat (LCHF) diets improve markers of metabolic health and can mitigate disease risk(Reference Mansoor, Vinknes and Veierod2) however, the mechanisms are poorly understood. We aimed to explore the effects of an ad libitum LCHF vs. high carbohydrate low fat (HCLF) diet on the plasma lipidome in 16 relatively healthy adults. Participants were randomly assigned to a HCLF diet (n = 8, ≥50% of energy from carbohydrates) or a LCHF diet (n = 8, consume <50 g/day of carbohydrates). Plasma samples were collected at 0, 4 and 8 weeks, and analysed for biomarkers of lipids and lipoprotein metabolism using high-throughput NMR spectroscopy platform. Data (mean ± SD) were subjected to 2 x 3-way mixed ANOVA. All the p-values are corrected for multiple testing via The Benjamini and Hochberg method. Dietary conditions did not differ in plasma triglyceride concentrations; however, triglycerides within HDL were significantly (P < 0.05) lower at week 4 (0.10 ± 0.03 mmol/L) compared with baseline (0.125 ± 0.05 mmol/L) and week 8 (0.119 ± 0.03 mmol/L) following the LCHF diet only. In contrast, the total phospholipids within LDL increased from baseline to week 8 with both the LCHF (0.72 ± 0.14 to 0.76 ± 0.12 mmol/L, P = 0.012) and HCLF (0.62 ± 0.16 to 0.68 ± 0.17 mmol/L, P = 0.031) diets leading to a significant interaction between diets (P < 0.001). Both diets resulted in increased total esterified cholesterol but only the HCLF diet increased within LDL at week 4 (1.48 ± 0.34 mmol/L, (P = 0.018) and week 8 (1.45 ± 0.41 mmol/L, (P = 0.008) compared with baseline (1.30 ± 0.37 mmol/L). Both dietary conditions impacted free cholesterol similarly although only the HCLF diet increased the free cholesterol within LDL from baseline to week 8 (0.48 ± 0.14 to 0.54 ± 0.15 mmol/L, P = 0.013) whereas no significant change was observed with the LCHF diet. Only the HCLF diet resulted in significant increases in total lipids within LDL from baseline to week 8 (2.53 ± 0.67 to 3.12 ± 0.50 mmol/L, P = 0.010) whereas no significant change was observed with the LCHF diet with no differences between diets. Similarly, no difference between groups was observed on lipoprotein particle concentration. However, LDL particle concentration significantly increased from baseline to week 8 (1071.47 ± 517.78 to 1302.54 ± 306.07 nmol/L, P = 0.027) following the HCLF diet whereas no change was observed with the LCHF diet. A HCLF diet can increase LDL lipids, cholesterol and particle concentrations that might lead to increased cardiometabolic risk(Reference Duran, Aday and Cook3).Conversely, a LCHF diet could decrease risks associated with lower HDL triglycerides(Reference Girona, Amigo and Ibarretxe4). However, longer term dietary studies with larger sample sizes in other ethnicities are warranted.

Low-carbohydrate high-fat (LCHF) diets can be just as effective as high-carbohydrate, lower-fat (HCLF) diets for improving cardiovascular disease risk markers. Few studies have compared the effects of the UK HCLF dietary guidelines with an LCHF diet on lipids and lipoprotein metabolism using high-throughput NMR spectroscopy. This study aimed to explore the effect of an ad libitum 8-week LCHF diet compared to an HCLF diet on lipids and lipoprotein metabolism and CVD risk factors. For 8 weeks, n = 16 adults were randomly assigned to follow either an LCHF (n = 8, <50 g CHO p/day) or an HCLF diet (n = 8). Fasted blood samples at weeks 0, 4, and 8 were collected and analysed for lipids, lipoprotein subclasses, and energy-related metabolism markers via NMR spectroscopy. The LCHF diet increased (p < 0.05) very small VLDL, IDL, and large HDL cholesterol levels, whereas the HCLF diet increased (p < 0.05) IDL and large LDL cholesterol levels. Following the LCHF diet alone, triglycerides in VLDL and HDL lipoproteins significantly (p < 0.05) decreased, and HDL phospholipids significantly (p < 0.05) increased. Furthermore, the LCHF diet significantly (p < 0.05) increased the large and small HDL particle concentrations compared to the HCLF diet. In conclusion, the LCHF diet may reduce CVD risk factors by reducing triglyceride-rich lipoproteins and improving HDL functionality.

BACKGROUND: Current cardiac rehabilitation (CR) practices focus on aerobic-style exercise with minimal nutrition advice. This approach may not be optimal for CR patients with reduced muscle mass and elevated fat mass. Higher protein, Mediterranean-style diets combined with resistance exercise (RE) may improve muscle mass and reduce the risk of future cardiovascular events, although such an approach is yet to be trialed in a CR population. OBJECTIVE: We explored patient perspectives on the proposed design of a feasibility study. Patients reflected on the acceptability of a proposed high-protein Mediterranean-style diet and RE protocol, emphasizing research methodology and the acceptability of the proposed recipes and exercises. DESIGN: We applied quantitative and qualitative (mixed methods) approaches. The quantitative approach involved an online questionnaire (n = 40) regarding the proposed study methodology and relevance. A subset of participants (n = 12) received proposed recipe guides and were asked to prepare several dishes and complete an online questionnaire regarding their experience. Another subset (n = 18) received links to videos of the proposed RE and completed a questionnaire regarding their impressions of them. Finally, semi-structured interviews (n = 7) were carried out to explore participants' impressions of the proposed diet and exercise intervention. RESULTS: Quantitative data indicated a high level of understanding of the intervention protocol and its importance within the context of this research. There was a high degree of willingness to participate in all aspects of the proposed study (>90%). The trialed recipes were enjoyed and found to be easy to make by a majority of participants (79 and 92.1%, respectively). For the proposed exercises 96.5% of responses agreed they would be willing to perform them and, 75.8% of responses agreed they would enjoy them. Qualitative analysis revealed that participants viewed the research proposal, diet, and exercise protocol in a positive light. The research materials were considered appropriate and well explained. Participants suggested practical recommendations for improving recipe guides and requested more individual-focused exercise recommendations, and more information on the specific health benefits of the diet and exercise protocols. CONCLUSION: The study methodology and the specific dietary intervention and exercise protocol were found to be generally acceptable with some suggested refinements.

Sarcopenia, once considered an inevitable consequence of ageing, is now recognised as a complex syndrome influenced by lifestyle, disease, and acute physiological stress. As global life expectancy rises, its prevalence is increasing, straining healthcare systems [1, 2] due to its association with disability, frailty, and comorbidities [3]. Prevalence estimates range from 0.2% to 86.5% depending on diagnostic criteria [4]. While typically studied in older adults, evidence suggests earlier onset, with rates between 8%-36% in those under 60 and 10%-27% in those aged 60 and older [4]. This variability partly reflects classification differences, with the European Working Group on Sarcopenia in Older People (EWGSOP2) [5] defining primary sarcopenia (ageing-related) and secondary sarcopenia (driven by disease, inactivity, or malnutrition), each posing distinct diagnostic challenges.

Cancer cachexia (CC) syndrome, a feature of cancer-associated muscle wasting, is particularly pronounced in older patients, and is characterised by decreased energy intake and upregulated skeletal muscle catabolic pathways. To address CC, appetite stimulants, anabolic drugs, cytokine mediators, essential amino acid supplementation, nutritional counselling, cognitive behavioural therapy, and enteral nutrition have been utilised. However, pharmacological treatments that have also shown promising results, such as megestrol acetate, anamorelin, thalidomide, and delta-9-tetrahydrocannabinol, have been associated with gastrointestinal and cardiovascular complications. Emerging evidence on the efficacy of probiotics in modulating gut microbiota also presents a promising adjunct to traditional therapies, potentially enhancing nutritional absorption and systemic inflammation control. Additionally, low-dose olanzapine has demonstrated improved appetite and weight management in older patients undergoing chemotherapy, offering a potential refinement to current therapeutic approaches. This review aims to elucidate the molecular mechanisms underpinning CC, with a particular focus on the role of anorexia in exacerbating muscle wasting, and to propose pharmacological and non-pharmacological strategies to mitigate this syndrome, particularly emphasising the needs of an older demographic. Future research targeting CC should focus on refining appetite-stimulating drugs with fewer side-effects, specifically catering to the needs of older patients, and investigating nutritional factors that can either enhance appetite or minimise suppression of appetite in individuals with CC, especially within this vulnerable group.

The consumption frequency and portion size of discretionary snacks are thought to contribute to a greater food intake and risk of overweight or obesity in the developed world but evidence from epidemiological studies is inconclusive. To investigate this, we systematically evaluated evidence on the effects of discretionary snack consumption on weight status, energy intake, and diet quality. Articles involving discretionary snacks reported against the outcome measures of any primary, peer-reviewed study using human participants from free-living conditions for all age groups were included. A total of 14,780 titles were identified and 40 eligible publications were identified. Three key outcomes were reported: weight status (n = 35), energy intake (n = 11), and diet quality (n = 3). Increased discretionary snack consumption may contribute modestly to energy intake, however, there is a lack of consistent associations with increased weight/BMI. Although cross-sectional analyses offered conflicting findings, longitudinal studies in adults showed a consistent positive relationship between discretionary snack intake and increasing weight or body mass index. Given that experimental findings suggest reducing the size of discretionary snacks could lead to decreased consumption and subsequent energy intake, food policy makers and manufacturers may find it valuable to consider altering the portion and/or packaging size of discretionary snacks.

This narrative review examines the mechanisms underlying the development of cardiovascular (CVD) and metabolic diseases (MDs), along with their association with sarcopenia. Furthermore, non-pharmacological interventions to address sarcopenia in patients with these conditions are being suggested. The significance of combined training in managing metabolic disease and secondary sarcopenia in type II diabetes mellitus is emphasized. Additionally, the potential benefits of resistance and aerobic training are being explored. This review emphasises the role of nutrition in addressing sarcopenia in patients with CVD or MDs, focusing on strategies such as optimising protein intake, promoting plant-based protein sources, incorporating antioxidant-rich foods and omega-3 fatty acids, and ensuring sufficient vitamin D levels. Moreover, the potential benefits of targeting gut microbiota through probiotics and prebiotic fibres in sarcopenic individuals are being considered. Multidisciplinary approaches that integrate behavioural science are explored to enhance the uptake and sustainability of behaviour-based sarcopenia interventions. Future research should prioritise high-quality randomized controlled trials to refine exercise and nutritional interventions and investigate the incorporation of behavioural science into routine practices. Ultimately, a comprehensive and multifaceted approach is essential to improve health outcomes, well-being, and quality of life in older adults with sarcopenia and coexisting cardio-vascular and metabolic diseases.